PROJECT SUMMARY The opioid epidemic has become entrenched in Ohio, with an age-adjusted opioid-related overdose death rate of 32.9/100,000 people (2017), ranking second nationally. Neither rural nor urban areas have been spared, with 38 of Ohio?s 88 counties (43%) reporting opioid-related deaths exceeding 25/100,000 people. Since 2012, Ohio has mounted an unprecedented effort to reduce opioid use disorder (OUD) morbidity and mortality through policies and investments in prevention, treatment, and recovery efforts. However, challenges inherent in integrating and deploying evidence-based interventions (EBI) across sectors has limited their impact in affected communities. The goal of Optimizing Healing in Ohio Communities (OHiO) is to systematically plan, implement, and evaluate data-driven approaches that integrate multi-pronged EBI within healthcare, behavioral health, justice systems, and communities to reduce opioid overdose deaths in 19 highly affected counties by 40% in 3 years. OHiO is anchored by three NCATS-funded CTSAs and the NIDA-funded Ohio Valley Node of the Clinical Trials Network and leverages extensive existing collaborations with community coalitions, state and county governments, and healthcare, behavioral health and criminal justice sectors. OHiO?s approach is based upon and aligned with the state-mandated Community Health Assessments and Community Health Improvement Plans, leveraging state and federally funded programs already in place. The overarching goal will be met through completion of three aims. Aim 1) Plan: We will assess current policies/programs regarding OUD, opioid misuse, and opioid-related fatalities; using the Exploration, Adoption/Preparation, Implementation and Sustainment model, work with communities to select EBI to reduce OUD and overdose deaths; and identify gaps in services/service coordination that are amenable to intervention. Aim 2) Implement: Through a pragmatic community-based clinical trial, we will deliver EBI packages using a cluster stepped-wedge design in which collaborating communities are randomized by the timing of which selected interventions are received. Aim 3) Evaluate: We will continuously collect and analyze data using the Reach, Efficacy, Adoption, Implementation, and Maintenance (RE-AIM) model to assess the impact of the integrated interventions and implementation outcomes including acceptability, adoption (including fidelity to the intervention), feasibility, penetration, and incremental cost and cost-effectiveness of the multipronged approach. We will also establish Learning Health Communities to provide community stakeholders access to real-time, actionable information. Ultimately, OHiO will provide rigorous and reproducible evidence of the effectiveness of integrated prevention, treatment, and recovery programs in the community context; an exportable and scalable model of service assessment, community-engaged decision-making; and integrated, data-driven EBI that can be implemented by affected communities in Ohio, the region, and across the US.